Neonatal Abstinence Syndrome (NAS)
Irritability in infants may be caused by Neonatal Abstinence Syndrome (NAS). Fetal drug exposure is a nationwide problem. The U.S. Department of Health and Human Services reported that in 2009-2010 nearly 4.5 percent of pregnant women exposed their unborn child to illicit drugs in utero, with greatest prevalence among teen pregnancies (15-17 years, 16.2%) and young adult pregnancies (18-25 years, 7.4%; compared to 26-44 years, 1.9%). Recent estimates of fetal exposure to licit drugs and prescription medications are also remarkable (10.8% alcohol; 16.3% tobacco), with a nearly five-fold increase in ante partum maternal opiate use between 2000 and 2009. NAS refers to drug withdrawal symptoms and multi-system disturbances that occur following termination of drug/s to which an infant has developed physical tolerance and dependence (e.g., observed at birth when fetal and maternal circulations are separated). Over 3% of every 1000 hospital births nationwide have been diagnosed with NAS (i.e., approximately one infant per hour) and upwards of 90% of drug-exposed newborns present with NAS. Hospitalization costs associated with treatment of NAS infants, excluding subsequent neurobehavioral and psychosocial care, are estimated at nearly $750 million annually in the United States.
NAS has been associated with sleep deprivation, disorganization and fragmentation. Fetal exposure to drugs commonly results in central, autonomic, vasomotor and gastrointestinal instabilities in the neonate. Respiratory complications have been identified as the most prevalent disturbance of withdrawal, e.g., increased apnea (i.e., long pauses in breathing that can result in blood-oxygen desaturation), irregular or periodic breathing and tachypnea. This is not surprising since the newborn respiratory oscillator is inherently vulnerable to respiratory dysrhythmias, and maternal smoking and other fetal drug exposure further compromise the developing respiratory control system by impairing central chemosensitivity and altering neurotransmitter systems and neural circuits.
Notably, drug withdrawing infants are at high risk for sudden infant death syndrome due to depressed ventilatory drive and abnormal respiratory patterning. Infant withdrawal symptoms also include persistent irritability marked by excessive movement, crying and sleep disruption, instability of heart rate (bradycardia and tachycardia), and problems with thermoregulation (sweating) and feeding (vomiting and diarrhea).
Approximately 7-9% of the 600 bed annual occupancy in the NICU/CCN at UMass Memorial comprises NAS newborn infants who require morphine for opiate withdrawal (non-iatrogenic). In 2010-2011, the average length of stay was six weeks at a cost of ˜$1100/day (i.e., nearly $2 million/year in NAS hospitalization costs). Tools that can alleviate drug withdrawal, reduce hospitalization, and improve outcomes in NAS are warranted.
While research has focused on factors that may affect symptoms and dysregulated neurobehaviors of NAS (e.g., drugs of exposure, epigenetic changes, genetic risks, socio-economic influences), precise pathophysiology has yet to be described and optimal intervention strategies remain inadequate. Novel approaches to the study and treatment of NAS are needed to facilitate weaning and minimize hospitalization compounded by prolonged pharmacological management, with implications for improved developmental outcomes and reduced medical costs for this at-risk population.
Colic
Irritability in infants may also be caused by colic. Infants who are diagnosed with colic do not suffer from a medical problem but generally experience episodes of crying that last more than three hours, on more than three days a week, for more than three weeks. Colic typically occurs in infants between two weeks and four months of age. It is estimated that up to twenty-five percent of infants may experience colic.
The cause of colic is generally unknown. Crying episodes resulting from colic usually begin at the same time of the day, often in the evening. The symptoms of colic often begin suddenly. Associated symptoms may include legs pulled up to the stomach, a flushed face, clenched hands, and a wrinkled brow. The cry is often high pitched and piercing.
Colic has been previously associated with intestinal causes. Colic, for example, may be triggered by foods or medicines passed through breast milk or by sensitivity to proteins in formula. Infants who have colic are very difficult to comfort and soothe.